The primary purpose of this application is to study the effects of diabetes mellitus on salivary glands and their innervation. Previous studies in our laboratory have shown a decrease in size of the submandibular gland of the male mouse due to diabetes. In addition, the granular tubules have less amylase granules, and less of the volume of the gland is occupied by ducts. We have observed a Schwann cell proliferation in trigeminal ganglia of the C67Bl/KsJ-Db mice of both sexes afflicted with the metabolic disturbance resembling human diabetes mellitus. The virtually identical genetic composition of the diabetic mutants and their normal littermates provide a useful experimental model for the evaluation of these effects. The changes observed in the salivary glands and the trigeminal ganglion could be relevant to the increased caries, periodontal involvement, thirst and dry mouth reported in uncontrolled diabetics. They could also be related to these manifestations of the disease in prediabetes and chemical diabetes. The secretory activity of the salivary glands, regulated by acetylcholinesterase-positive parasympathetic fibers from branches of the fifth, seventh, ninth and tenth cranial nerves, will be assessed by examining the fibers with a precise histochemical method for acetylcholinesterase developed in our laboratory and with the electron microscope. The changes in the ductal portions of the submandibular gland in mouse diabetes will be evaluated histo- and cytologically with a method to demonstrate amylase granules. In acinar cells and ductal portions they will be evaluated histo- and cytochemically with a method for the demonstration of the cytochrome oxidase of their mitochondria for both light and electron microscopy. Correlative studies of the diabetic status of the mice and the extent of their peripheral neuropathy, especially as it affects the trigeminal ganglion, and trigeminal and facial nerves will be performed by methods currently in use in our laboratory.